Clinical studies have demonstrated the potential of cancer immune therapy using adoptively transferred T cells or tumor vaccines. Although these have achieved marked response in some patients, they have fallen short of expectations in others. The success of cell-mediated immune rejection mechanisms depends in part on the ability of effector cells to adequately infiltrate tumors. Yet, the mechanisms governing homing of effector cells into tumors remain poorly understood. Specifically, the role of endothelium in T cell homing to tumors has not been elucidated to date.
Evidence exists that a variety of solid human tumors, including melanoma, gastrointestinal, breast, lung and ovarian cancer, are spontaneously infiltrated by T cells. Within each tumor type, the intensity of tumor-infiltrating T cells may vary significantly, and brisk T cell infiltrate has been associated with improved prognosis. For example, T cells infiltrating tumor islets (intraepithelial T cells) are detected only in a select group of patients in ovarian cancer. These patients exhibit markedly improved progression-free and overall survival, a finding recently confirmed by others.
Methods for improving cancer vaccine immunotherapy are urgently needed in the art.